TY - JOUR
T1 - Gender and age normalization and ventilation efficiency during exercise in heart failure with reduced ejection fraction
AU - group, on behalf of MECKI score research
AU - Salvioni, Elisabetta
AU - Corrà, Ugo
AU - Piepoli, Massimo
AU - Rovai, Sara
AU - Correale, Michele
AU - Paolillo, Stefania
AU - Pasquali, Mario
AU - Magrì, Damiano
AU - Vitale, Giuseppe
AU - Fusini, Laura
AU - Mapelli, Massimo
AU - Vignati, Carlo
AU - Lagioia, Rocco
AU - Raimondo, Rosa
AU - Sinagra, Gianfranco
AU - Boggio, Federico
AU - Cangiano, Lorenzo
AU - Gallo, Giovanna
AU - Magini, Alessandra
AU - Contini, Mauro
AU - Palermo, Pietro
AU - Apostolo, Anna
AU - Pezzuto, Beatrice
AU - Bonomi, Alice
AU - Scardovi, Angela B.
AU - Filardi, Pasquale Perrone
AU - Limongelli, Giuseppe
AU - Metra, Marco
AU - Scrutinio, Domenico
AU - Emdin, Michele
AU - Piccioli, Lucrezia
AU - Lombardi, Carlo
AU - Cattadori, Gaia
AU - Parati, Gianfranco
AU - Caravita, Sergio
AU - Re, Federica
AU - Cicoira, Mariantonietta
AU - Frigerio, Maria
AU - Clemenza, Francesco
AU - Bussotti, Maurizio
AU - Battaia, Elisa
AU - Guazzi, Marco
AU - Bandera, Francesco
AU - Badagliacca, Roberto
AU - Di Lenarda, Andrea
AU - Pacileo, Giuseppe
AU - Passino, Claudio
AU - Sciomer, Susanna
AU - Ambrosio, Giuseppe
AU - Agostoni, Piergiuseppe
PY - 2019/11/11
Y1 - 2019/11/11
N2 - Aims: Ventilation vs. carbon dioxide production (VE/VCO2) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. Methods and results: We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13–83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 <14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2-year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 <14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). Conclusions: The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.
AB - Aims: Ventilation vs. carbon dioxide production (VE/VCO2) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. Methods and results: We calculated the linear regressions between age and VE/VCO2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13–83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO2 14.8 ± 4.9, mL/min/kg, VE/VCO2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO2 <14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO2 = 0.052 × Age + 23.808 (r = 0.192); male, VE/VCO2 = 0.095 × Age + 20.227 (r = 0.371) (P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO2 values. The 2-year survival prognostic power of VE/VCO2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO2 <14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). Conclusions: The percentage of predicted VE/VCO2 slope value strengthens the prognostic power of VE/VCO2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.
KW - Cardiopulmonary exercise test
KW - Heart failure
KW - Prognosis
KW - Ventilation efficiency
U2 - 10.1002/ehf2.12582
DO - 10.1002/ehf2.12582
M3 - Article
JO - ESC heart failure
JF - ESC heart failure
SN - 2055-5822
ER -